Article Text

Download PDFPDF

1526 Nous-209 genetic vaccine encoding shared cancer neoantigens is safe and elicits robust immune response in healthy Lynch syndrome carriers: interim results from Phase 1 cancer interception trial
  1. Morena D’Alise1,
  2. Jason Willis2,
  3. Guido Leoni1,
  4. Marcia Cruz-Correa3,
  5. Michael J Hall4,
  6. Gregory E Idos5,
  7. Irene Garzia1,
  8. Laura Antonucci1,
  9. Gabriella Cotugno1,
  10. Loredana Siani1,
  11. Sven Gogov6,
  12. Diane Liu7,
  13. Jack Lee7,
  14. Lana A Vornik8,
  15. Laura Reyes Uribe8,
  16. Araceli Garcia-Gonzalez8,
  17. Ellen Richmond9,
  18. Asad Umar9,
  19. Powel H Brown8,
  20. Luz Maria Rodriguez9,10,
  21. Elisa Scarselli1 and
  22. Eduardo Vilar8
  1. 1Nouscom Srl, Rome, Italy
  2. 2Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
  3. 3University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico
  4. 4Fox Chase Cancer Center, Philadelphia, PA, USA
  5. 5City of Hope Comprehensive Cancer Center, Duarte, CA, USA
  6. 6Nouscom AG, Basel, Switzerland
  7. 7Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
  8. 8Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
  9. 9National Cancer Institute, Bethesda, MD, USA
  10. 10Department of Surgery, Walter Reed National Military Medical Center, Bethesda, MD, USA
  • Journal for ImmunoTherapy of Cancer (JITC) preprint. The copyright holder for this preprint are the authors/funders, who have granted JITC permission to display the preprint. All rights reserved. No reuse allowed without permission.


Background Microsatellite instability (MSI) tumors are characterized by defects in the DNA mismatch repair (MMR) genes that lead to the accumulation of mutations within microsatellite (MS) loci. Indels in MS regions of coding genes can result in the synthesis of shared frameshift peptide (FSP) neoantigens, expected to be immunogenic and safe. MSI tumors develop sporadically or secondary to hereditary predisposition as part of Lynch Syndrome (LS), one of the most common hereditary colorectal cancers. Nous-209 is a genetic vaccine encoding 209 neoantigens shared across sporadic and hereditary MSI tumors developed for interception and treatment of MSI tumors.1 A phase I trial (NCT04041310) combining the Nous-209 vaccine with pembrolizumab anti-PD-1 antibody has been recently completed in metastatic colorectal, gastric and gastro-esophageal cancer patients showing excellent safety, immunogenicity, and promising signs of clinical efficacy.2 3 Here, we report the safety and immunogenicity of Nous-209 from the Phase Ib/II trial in LS carriers for the first 10 subjects.

Methods NCT05078866 is a Phase Ib/II single-arm, open-label, clinical trial testing Nous-209 monotherapy for immune-interception in LS carriers. Safety and immunogenicity are the co-primary objectives. Nous-209 is administered intramuscularly: one prime with a Great Ape Adenovirus (GAd20-209-FSPs) on day 1, and boost with a Modified Vaccinia Ankara (MVA-209-FSPs) at week 8. Blood samples are collected for biomarker assays (Baseline, weeks 3, 8, 9, 24, and 52). Immunogenicity is evaluated on PBMC before and after vaccination by ex-vivo IFNγ ELISpot assay.

Results On the data cutoff date (28 May 2023), 21 patients were enrolled in this NCI-sponsored study, 18 of those treated with both GAd and MVA. No dose limiting serious adverse events (SAEs) were observed (n=10), and the treatment appears safe and well tolerated. Immunogenicity was demonstrated in 100% of tested patients (n=10) with a mean peak response of ~700 IFN-γ SFCs/million PBMCs. No immune responses were detected at baseline prior vaccination in either previvors or survivors LS carriers. Nous-209-induced T cell responses were broad, recognizing different FSPs with induction of both CD4 and CD8 T cell responses. Deconvolution of T cell responses against predicted CD8 epitopes included in the FSPs pools showed multiple positive responses, confirming the optimal breadth of immune responses.

Conclusions Nous-209 is safe, well tolerated, and elicits potent and broad immune response in both LS carriers previvors and survivors, supporting Nous-209 development as a compelling approach for LS cancer interception.


  1. Leoni G, et al. A genetic vaccine encoding shared cancer neoantigens to treat tumors with microsatellite instability. Cancer Res. 2020;80(18):3972–3982.

  2. Fakih M, et al. First clinical and immunogenicity results including all subjects enrolled in a phase I study of Nous-209, an off-the-shelf immunotherapy, with pembrolizumab, for the treatment of tumors with a deficiency in mismatch repair/microsatellite instability (dMMR/MSI). Journal of Clinical Oncology 2022;40(16_suppl):2515–2515.

  3. D’Alise AM, et al. Adenoviral-based vaccine promotes neoantigen-specific CD8+ T cell stemness and tumor rejection. Science Translational Medicine 2022;14(657):eabo7604.

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.